Genetic markers linking risk for type 2 diabetes and Alzheimer’s identified

Certain patients with type 2 diabetes may have specific genetic risk factors that put them at higher risk for developing Alzheimer’s disease, according to a study conducted at the Icahn School of Medicine at Mount Sinai.

Under the leadership of Giulio Maria Pasinetti, MD, PhD, the study team used recent genome wide association study (GWAS) findings to investigate whether type 2 diabetes and Alzheimer’s disease share common genetic etiological factors and the potential impact of these genetic factors on the cellular and molecular mechanisms that may contribute to the development of both these diseases.  

GWAS look at differences at many points in the genetic code to see if, across a population, one or more variations in the code are found more often in those with a given trait. Even the smallest genetic variations, called single nucleotide polymorphisms (SNPs), can have a major impact on a trait by swapping just one of the 3.2 billion “letters” that make up the human DNA code.

One of the major long-term complications of type 2 diabetes is an increased risk for developing Alzheimer’s disease. While previous studies strongly suggested a causative role of diabetes in the onset and progression of Alzheimer’s disease dementia, the specific mechanistic interactions connecting diabetes and Alzheimer’s disease had not been previously described.  

“We identified multiple genetic differences in terms of SNPs that are associated with higher susceptibility to develop type 2 diabetes as well as Alzheimer’s disease,” says Dr Pasinetti. “Many of these SNPs are traced to genes whose anomalies are known to contribute to type 2 diabetes and Alzheimer’s disease, suggesting that certain diabetic patients with these genetic differences are at high risk for developing Alzheimer’s. Our data highlights the need for further exploration of genetic susceptibility to Alzheimer’s disease in patients with type 2 diabetes.”

Study outcomes could lead to development of type 2 diabetes therapies that may also help prevent subsequent development of Alzheimer’s

An estimated 312 million people suffer from type 2 diabetes worldwide while Alzheimer’s disease affects nearly 45 million people worldwide. There is currently no cure for either condition.  

Mounting evidence suggests that Alzheimer’s disease dementia can be traced back to pathological conditions that are initiated several decades before clinical Alzheimer’s disease onset. Since type 2 diabetes is one of the potentially modifiable risk factors for Alzheimer’s disease, it is critically important for scientists to uncover the genetics of this complex connection so that new therapeutic interventions may be developed and targeted to at-risk individuals with type 2 diabetes prior to the onset of Alzheimer’s disease dementia.

This study will support ongoing research applications to further explore genetic susceptibility in patients with type 2 diabetes for developing Alzheimer’s disease and help improve the design of future novel treatments for a subpopulation of type 2 diabetes subjects with genetic predisposition to Alzheimer’s disease, which could benefit type 2 diabetes and reduce the risk for subsequent development of Alzheimer’s disease.

The study findings are published in Molecular Aspects of Medicine.